Ulcerative Colitis: Reinshagen M

Reinshagen M, Von Tirpitz C. · Department of Medicine I, University of Ulm, Ulm, Germany. · Minerva Med. · Pubmed #15785433 No free full text.

Abstract: Osteoporosis is a frequent finding in patients with Crohn's disease and ulcerative colitis. The prevalence of vertebral fractures in those patients with significantly reduced bone mineral density is up to 22%. Factors contributing to osteoporosis in inflammatory bowel disease (IBD) patients are treatment with glucocorticoids, increased cytokine production by the inflammation itself, malabsorption and possibly hypogonadism. Therefore, consequent treatment of the underlying IBD and minimising therapy with systemic glucocorticoids, as well as the adequate intake of calcium and vitamin D, may be very important measures to prevent bone loss in IBD. In patients with osteoporosis associated with Crohn's disease or ulcerative colitis, various treatment strategies, such as sodium fluoride and aminobisphosphonates, are discussed. Unfortunately, interventional studies in secondary osteoporosis are often limited by the small study population. The efficacy in prevention of vertebral fractures is not proven in any of the described treatment modalities in these patients. Therefore, guidelines are based on data using bone density as the most accepted surrogate marker and treatment guidelines are based on data from patients with postmenopausal and steroid-induced osteoporosis.

Hoffmann JC, Zeitz M, Bischoff SC, Brambs HJ, Bruch HP, Buhr HJ, Dignass A, Fischer I, Fleig W, Fölsch UR, Herrlinger K, Höhne W, Jantschek G, Kaltz B, Keller KM, Knebel U, Kroesen AJ, Kruis W, Matthes H, Moser G, Mundt S, Pox C, Reinshagen M, Reissmann A, Riemann J, Rogler G, Schmiegel W, Schölmerich J, Schreiber S, Schwandner O, Selbmann HK, Stange EF, Utzig M, Wittekind C. · Medizinische Klinik I mit Schwerpunkt Gastroenterologie/Infektiologie/Rheumatologie, Charité, Universitätsmedizin Berlin. · Z Gastroenterol. · Pubmed #15455267 No free full text.

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Kruis W, Dignass A, Steinhagen-Thiessen E, Morgenstern J, Mössner J, Schreiber S, Vecchi M, Malesci A, Reinshagen M, Löfberg R. · Evangelisches Krankenhaus Kalk, Innere Abteilung, Universität zu Köln, Germany. · World J Gastroenterol. · Pubmed #16437606 links to  free full text

Abstract: AIM: To study the efficacy, safety, and feasibility of a granulocyte adsorptive type apheresis system for the treatment of patients with chronically active ulcerative colitis despite standard therapy. METHODS: An open label multicenter study was carried out in 39 patients with active ulcerative colitis (CAI 6-8) despite continuous use of steroids (a minimum total dose of 400 mg prednisone within the last 4 wk). Patients received a total of five aphereses using a granulocyte adsorptive technique (Adacolumn (reg), Otsuka Pharmaceutical Europe, UK). Assessments at wk 6 and during follow-up until 4 mo comprised clinical (CAI) and endoscopic (EI) activity index, histology, quality of life (IBDQ), and laboratory tests. RESULTS: Thirty-five out of thirty-nine patients were qualified for intent-to-treat analysis. After the apheresis treatment at wk 6, 13/35 (37.1%) patients achieved clinical remission and 10/35 (28.6%) patients had endoscopic remission (CAI<4, EI<4). Quality of life (IBDQ) increased significantly (24 points, P<0.01) at wk 6. Apheresis could be performed in all but one patient. Aphereses were well tolerated, only one patient experienced anemia. CONCLUSION: In patients with steroid refractory ulcerative colitis, five aphereses with a granulocyte/monocyte depleting filter show potential short-term efficacy. Tolerability and technical feasibility of the procedure are excellent.

Holtmann MH, Krummenauer F, Claas C, Kremeyer K, Lorenz D, Rainer O, Vogel I, Böcker U, Böhm S, Büning C, Duchmann R, Gerken G, Herfarth H, Lügering N, Kruis W, Reinshagen M, Schmidt J, Stallmach A, Stein J, Sturm A, Galle PR, Hommes DW, D'Haens G, Rutgeerts P, Neurath MF. · First Department of Medicine, Johannes Gutenberg University, Mainz, Germany. · Dig Dis Sci. · Pubmed #16927148 No free full text.

Abstract: In Crohn's disease the optimal duration of azathioprine treatment is still controversial and for ulcerative colitis only limited data are available to support its efficacy. Charts of 1176 patients with IBD from 16 European centers were analyzed. Flare incidences and steroid dosages were assessed for the time before and during treatment and after discontinuation. Within the first 4 years, azathioprine suppressed flare incidence and steroid consumption in both diseases (P < 0.001). While in CD discontinuation after 3-4 years did not lead to reactivation, this was the case in UC. However, continuation beyond 4 years further improved clinical activity in CD and steroid requirement in both diseases (P < 0.001). Discontinuation of azathioprine may thus be considered after 3-4 years in CD patients in complete remission without steroid requirement. In all other CD patients and for UC patients in general, continuation seems beneficial. These results support a novel differential algorithm for long-term azathioprine therapy in IBD.

Reinshagen M, Fölsch UR. · Abt. Innere Medizin I, Universität Ulm. · Z Gastroenterol. · Pubmed #15455279 No free full text.

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Ebinger M, Leidl R, Thomas S, Von Tirpitz C, Reinshagen M, Adler G, Konig HH. · Department of Health Economics, University of Ulm, Germany. · J Gastroenterol Hepatol. · Pubmed #14731130 No free full text.

Abstract: BACKGROUND AND AIM: Because of its long duration, inflammatory bowel disease (IBD) causes high use of health services and high lifetime costs for medical care. The aim of the present study was to measure the costs of outpatient care in patients with IBD in a German University Hospital and to identify potentially relevant determinants of costs. METHODS: The use of resources of 599 outpatient patients treated at a German University Hospital (65% Crohn's disease [CD] and 26% ulcerative colitis [UC]) was measured using a routine database. Costs of medical services (diagnostics and treatment) were considered as well as costs of medication. Resource use was valued using fee schedules for hospital services and pharmacy prices for drugs. RESULTS: The mean cost of one outpatient visit was Euros 162, including physician costs, laboratory costs, and costs of diagnostic procedures following the visit. For a subgroup of 272 patients, the mean annual cost for outpatient care was Euros 3171. Medication accounted for 85% of the total annual costs. Potential determinants, such as main diagnosis (CD or UC), sex, age, localization of disease, and occurrence of anemia, had no influence on costs, whereas complications of IBD and use of corticosteroids showed an impact on annual costs. CONCLUSIONS: This is the first time that the structure and range of outpatient treatment costs for IBD have been demonstrated for a German hospital.

von Tirpitz C, Steder-Neukamm U, Glas K, Sander S, Ring C, Klaus J, Reinshagen M. · Abteilung Innere Medizin I, Universitätsklinikum Ulm. · Z Gastroenterol. · Pubmed #14661123 No free full text.

Abstract: INTRODUCTION: Osteoporosis is a frequent and clinically important complication in inflammatory bowel disease (IBD). Prevalence and risk factors have been examined in small numbers of patients. With a nationwide survey of members of the German Crohn's and Ulcerative Colitis Association (DCCV) we wanted to evaluate the situation in a larger group of patients. METHODS: Questionnaires were sent with the autumn issue of the members journal to approx. 14,620 affected members of the DCCV. Items covered osteoporosis, clinical symptoms, anamnesis and sociodemographic topics. Results are presented as descriptive analysis and in a logistic regression analysis of factors contributing to the osteoporosis risk. RESULTS: 2,536 questionnaires could be used (17.3 %). Mean age and distribution concerning diagnosis and gender were comparable to the DCCV members in total. The prevalence of pathologic bone density was 62.3 % in those 1,265 patients (50.1 %) who underwent bone densitometry in the course of their disease. The analysis led to the following possible risk factors: disease activity (high chronic activity or more than 1 acute flare annually vs. remission, p < 0.001), lifetime steroid dosage > 10 g (p = 0.002), Crohn's disease vs. ulcerative colitis (p = 0.02), multiple bowel resection (p = 0.032), age (p = 0.018) and low body mass index (p = 0.034). 83.4 % of the patients with pathologic bone density received specific therapy, but most of those (63.5 %) were solely substituted with calcium and vitamin D. CONCLUSION: This is the first study looking at epidemiology and risk factors of osteoporosis in a large study population of patients with inflammatory bowel disease. Although the prevalence may be overestimated due to selection bias in our study, osteoporosis is confirmed as a frequent and clinically relevant complication in IBD. Bone densitometry is recommended in those patients with one or more risk factors.

König HH, Ulshöfer A, Gregor M, von Tirpitz C, Reinshagen M, Adler G, Leidl R. · Department of Health Economics, University of Ulm, Germany. · Eur J Gastroenterol Hepatol. · Pubmed #12439115 No free full text.

Abstract: OBJECTIVE: The EuroQol EQ-5D is a generic questionnaire for describing and valuing patients' health-related quality of life. The purpose of the study was to analyse the construct validity, criterion validity, test-retest reliability and responsiveness of the EQ-5D in patients with inflammatory bowel disease. METHODS: 152 consecutive patients with inflammatory bowel disease (123 with Crohn's disease and 29 with ulcerative colitis) completed the EQ-5D, the SF-36 and the Inflammatory Bowel Disease Questionnaire (IBDQ). Of the study group, 66 patients filled in the EQ-5D a second time after a 2-week gap, including a transition question. Disease activity was measured by the Crohn's Disease Activity Index (CDAI) and by Rachmilewitz's Clinical Activity Index (CAI). RESULTS: The EQ-5D showed a moderate ceiling effect. Correlation between the EQ-5D visual analogue scale (EQ VAS) score and CDAI/CAI was r = -0.65/r = -0.71 (both P < 0.001). Levels of responses to EQ-5D items and the EQ VAS score were significantly better for patients in remission than for patients with active disease (all P < 0.01). For the total sample, coefficients of correlation between the EQ VAS score and SF-36 and IBDQ scores ranged between 0.37 and 0.73 (all P < 0.0001). When repeated, the EQ-5D was reliable in stable patients (intraclass correlation coefficient for EQ VAS = 0.77, kappa statistic for items 0.39 to 1.00); the EQ VAS was responsive in patients who, in the transition question, indicated an improvement in health state (effect size 0.79). CONCLUSIONS: The EQ-5D is reasonably valid, reliable and responsive in patients with inflammatory bowel disease. It can be used to generate preference-based valuations of health-related quality of life in inflammatory bowel disease.

Heinzlmann M, Lang SM, Neynaber S, Reinshagen M, Emmrich J, Stratakis DF, Heldwein W, Wiebecke B, Loeschke K. · Department of Internal Medicine, Medizinische Klinik Innenstadt, University of Munich, D-80336 Munich, Germany. · Eur J Gastroenterol Hepatol. · Pubmed #12362095 No free full text.

Abstract: OBJECTIVES: Molecular screening for frequently mutated genes may increase the likelihood of identifying cancer risk groups, such as patients with longstanding inflammatory bowel disease. This study investigated the prevalence and time course of p53 and K-ras mutations in colonic lavage fluid of patients with inflammatory bowel disease. METHODS: Colonic lavage fluid from 190 patients with ulcerative colitis (73), Crohn's disease (58) or controls (49 non-tumour, 10 colorectal cancer) was studied by oligomer-specific hybridization for K-ras mutations and single-strand conformation polymorphism (SSCP) for p53 mutations. Follow-up investigations were carried out after 1-3 years. RESULTS: Mutations were most frequent in carcinomas (5/10, 50%) and rare in non-tumour controls (1/49, 2.0%). They were found in Crohn's colitis in 15.4%, in extensive ulcerative colitis in 18.6%, in left-sided ulcerative colitis in 13.3%, and in distal ulcerative colitis in 6.7% (P > 0.05). There was a positive association with disease duration (> or =11 years, P < 0.05). Follow-up investigations detected the same mutation in four patients and revealed new mutations in three patients. CONCLUSIONS: In our large series of patients with inflammatory bowel disease, K-ras and p53 mutations could be detected with reasonable frequency and confirmed at follow-up in at least some patients. Our data encourage the use of molecular screening for the detection of malignant precursor lesions in at-risk patients.

Rösch M, Leidl R, Tirpitz C, Reinshagen M, Adler G, König HH. · Abteilung Gesundheitsökonomie, Universität Ulm, Germany. · Z Gastroenterol. · Pubmed #11961730 No free full text.

Abstract: OBJECTIVE: Cost diaries administered by patients have been used as a method to measure costs for different diseases. Our aim was to test the application of a patient cost diary in patients with inflammatory bowel disease (IBD) and to measure disease specific resource utilization and costs. PATIENTS AND METHODS: A specific patient cost diary for IBD was developed and tested in a prospective pilot study. 105 outpatients with IBD of a University Hospital agreed to participate over a 4 week follow-up period. They were asked to report weekly their use of medical care and costs related to their illness. Visits to health care providers, hospitalizations, drug use, costs due to absence from paid and unpaid work, travel costs as well as out-of-pocket expenses were considered. RESULTS: The response rate was 90 %. Almost 70 % of the patients estimated the diary as easy to fill in. Compared with other data sources, the cost measurement using the cost diary showed good agreement regarding costs of drug therapy and outpatient hospital treatment.Mean costs due to illness were estimated to be 1,500 Euro per 4 weeks. This corresponds to total costs of about 20,000 Euro per year of care. 69 % of total costs were indirect costs due to illness-related absence from work, days of inactivity at home, and early retirement. Direct health care and direct non health care costs (e. g. travel costs) were responsible for 27 % and 4 % of costs, respectively. DISCUSSION AND CONCLUSION: The presented instrument offers a suitable and practical method of assessing IBD-related resource utilization. The prospectively obtained data for direct medical and non medical, as well as indirect costs allow a cost measurement from the societal perspective. The presented cost diary can be used for measuring costs for economic evaluations of medical interventions.

Rösch M, Leidl R, Thomas S, von Tirpitz C, Reinshagen M, Adler G, König HH. · Abteilung Gesundheitsökonomie, Medizinische Universitäts- und Poliklinik, Universität Ulm. · Med Klin (Munich). · Pubmed #11957787 No free full text.

Abstract: OBJECTIVE: To create a concept for measuring and valuating resource utilization of outpatient treatment of patients with inflammatory bowel disease in a German university hospital. MATERIAL AND METHODS: The measurement of health services was achieved using a computer-based routinely administered data base of the Medical Department. Measuring costs was performed in three steps: 1. identification of the categories of resource utilization, 2. quantitative measurement of resource use, 3. monetary valuation of the utilization of resources using German fee schedules and prices for drugs. RESULTS: The resource utilization of 272 patients with a treatment period of more than 1 year could be identified in a structured form. Categories of resource use could be identified and quantitatively measured as follows: anamnesis and physical examination by a physician in 100% of the visits, laboratory tests in 87.1%, endoscopic or sonographic services in 36.9%, and radiologic procedures in 14.1%. In 93.6% of the visits a medication was prescribed. Annual costs of outpatient care provided by the hospital were 3,171 [symbol: see text] per patient. Medication accounted for 85% of total costs. Analyzing the costs of medical treatment, mesalazine was the major cost component (48%), followed by budesonide (15%). CONCLUSION: The presented concept offers a good access to measure costs of outpatient treatment of patients with inflammatory bowel disease. It is suitable for measuring costs in the economic evaluation of alternative treatments or diagnostic strategies in an outpatient setting. It furthermore may be used as a component in cost-of-illness studies. For transferring the concept to other hospitals, the availability of a routine documentation of services should be checked. For economic analysis, a further data management is required.

Riedl S, Tandara A, Reinshagen M, Hinz U, Faissner A, Bodenmüller H, Buhr HJ, Herfarth C, Möller P. · Department of Surgery, University of Heidelberg, Germany. · Int J Colorectal Dis. · Pubmed #11686525 No free full text.

Abstract: Tenascin-C is a multifunctional matrix protein that is induced in inflammation and neoplasia. In the colonic mucosa of ulcerative colitis patients tenascin-C indicates tissue repair, and mucosal concentrations are correlated with local disease activity. We prospectively examined the relationship between serum concentrations of tenascin-C parameters of disease activity in surgically treated patients with ulcerative colitis and patients with inflammatory bowel disease (IBD). Perioperative serum concentrations were quantified by ELISA in 58 patients admitted for restorative proctocolectomy; controls were 37 patients with familial adenomatous polyposis receiving the same treatment. We also measured tenascin-C serum levels in 47 patients with ulcerative colitis and Crohn's disease who were receiving nonsurgical treatment. Preoperative serum tenascin-C levels were significantly higher in ulcerative colitis patients than in controls (17.2 +/- 14.6 microg/ml vs. 3.2 +/- 1.7 microg/ml) and were significantly correlated with clinical and histological parameters of disease activity; levels decreased significantly after restorative proctocolectomy. Serum tenascin-C levels were also correlated with the course of disease activity in conservatively treated IBD patients. Tenascin-C is thus not disease-specific. However, it does indicate the activity of IBD and may reflect the degree of tissue remodeling. The tenascin-C levels therefore offers a novel serum parameter for assessing disease activity and monitoring therapy in patients with IBD.

Mayer D, Reinshagen M, Mason RA, Muche R, von Tirpitz C, Eckelt D, Adler G, Beckh K, Kratzer W. · Abteilung Innere Medizin I, Universität Ulm. · Z Gastroenterol. · Pubmed #10820861 No free full text.

Abstract: Inflammatory bowel disease (IBD) is associated with morphological changes of the bowel wall that can be visualized by abdominal ultrasound (US). This method is a tool to detect the extent of bowel wall thickening and the length of involved segments. The purpose of this study was to determine the value of sonographic measurement of inflamed bowel wall segments as a quantitative parameter for disease activity. 137 patients with Crohn's disease (CD) and 32 patients with ulcerative colitis (UC) were included in the present study. A total 356 US examinations were performed within a one-year period. In a segment-by-segment analysis we determined the "volume of inflamed bowel wall" (VIB) by measuring wall thickness and longitudinal extent of pathologically altered bowel segments. VIB was used as a quantitative parameter for disease activity based on sonomorphological findings. At the same time the following parameters were also determined: CD activity index (CDAI) in patients with CD, clinical activity index (CAI) in patients with UC, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). We found no relevant correlation between VIB and biochemical indices of inflammation (ESR, CRP) and between VIB and clinical activity of IBD (CDAI, CAI). All correlation coefficients were below 0.5. It can be concluded that the extent of inflammatory changes of the bowel wall detected by US is not strictly associated with clinical activity and laboratory parameters of inflammation.

Reinshagen M, Glasbrenner B, Adler G. · Innere Medizin I der Universität Ulm. · Med Klin (Munich). · Pubmed #10603737 No free full text.

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Von Tirpitz C, Pischulti G, Klaus J, Rieber A, Brückel J, Böhm BO, Adler G, Reinshagen M. · Abteilung Innere Medizin I, Universitätsklinikum Ulm. · Z Gastroenterol. · Pubmed #10091278 No free full text.

Abstract: INTRODUCTION: Osteopenia and osteoporosis are frequent but often underestimated complications in inflammatory bowel disease. In patients with IBD, several factors could contribute to osteopenia, but the pathogenetic mechanisms are still not completely understood. We carried out a prospective study to evaluate the prevalence and possible etiologic factors for osteopenia and subsequent osteoporosis in IBD-patients. METHODS: 140 patients with inflammatory bowel disease (Crohn's disease n = 125, ulcerative colitis n = 15) underwent clinical and spine radiological assessments. Lumbar bone mineral densities were measured by dual energy X-ray absorptiometry (DXA). Markers of bone formation and resorption and vitamin D were assessed in n = 95 patients. Patients were asked about medication, previous or actual intestinal stenosis, smoking and intestinal resection. A lactose-H2-breath test was undertaken if lactose intolerance was clinically suspected. RESULTS: Compared to age- and sex-matched healthy controls (Z-score), the prevalence of osteopenia (Z < -1) was 62%, while osteoporosis (Z < -2) occurred in 38%. The mean bone density of IBD-patients was osteopenic with no significant differences between Crohn's disease (Z = -1.24) and ulcerative colitis (Z = -1.25). Osteoporotic fractures were seen in three patients (2.1%). Crohn's disease patients with osteoporosis showed a significant lower body mass index (BMI) than patients with normal bone density. 52.9% of patients with manifest osteoporosis underwent systemic steroid treatment in the preceding year, but only 34% of those with normal bone density. Except hemoglobin, none of the biochemical markers showed a significant difference between osteoporosis, osteopenia and patients with normal bone density. CONCLUSION: The results show a high prevalence of osteopenia and osteoporosis in IBD. Since osteoporosis is often associated with low body mass index, multiple intestinal resections and previous systemic steroid treatment, we suggest a bone densitometry in these patients. Since etiology of osteoporosis in IBD is multifactorious and not completely understood, there is still no standard treatment. The effect of osteoanabolic and antiresorptive agents must be evaluated in further studies.

Reinshagen M. · No affiliation provided · N Engl J Med. · Pubmed #16575949 No free full text.

This publication has no abstract.